CD69+CD103+CD8+ tissue-resident memory T cells possess stronger anti-tumor activity and predict better prognosis in colorectal cancer

被引：3

作者：

Wu, Zi-Xin ^{[1
]}

Da, Tian-Tian ^{[2
]}

Huang, Chuan ^{[2
]}

Wang, Xiao-Qing ^{[2
]}

Li, Liang ^{[2
]}

Zhao, Zhi-Bin ^{[2
]}

Yin, Ting-Ting ^{[1
]}

Ma, Hai-Qing ^{[2
]}

Lian, Zhe-Xiong ^{[2
]}

Long, Jie ^{[2
]}

Wang, Fei ^{[3
]}

Cao, Jie ^{[1
]}

机构：

[1] South China Univ Technol, Affiliated Hosp 2, Sch Med, Dept Gen Surg ,Guangzhou Digest Dis Ctr, Guangzhou 510180, Guangdong, Peoples R China

[2] Southern Med Univ, Guangdong Prov Peoples Hosp, Guangdong Acad Med Sci, Med Res Inst, Guangzhou 510080, Guangdong, Peoples R China

[3] Southern Med Univ, Guangdong Prov Peoples Hosp, Guangdong Cardiovasc Inst, Guangdong Acad Med Sci, Guangzhou 510080, Guangdong, Peoples R China

来源：

CELL COMMUNICATION AND SIGNALING | 2024年 / 22卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Colorectal cancer; Tissue-resident memory T cell; CD69; CD103; Anti-tumor effect; Prognosis; DIFFERENTIATION; SURVIVAL; IMMUNITY; MARKER;

D O I：

10.1186/s12964-024-01990-3

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

BackgroundColorectal cancer (CRC) is one of the most prevalent cancers worldwide. Despite advancements in therapeutic methodologies, it still causes a high rate of patient mortality. CD8+ tissue-resident memory T (TRM) cells are strategically positioned to mediate effective anti-tumor responses. However, the characteristic surface molecules and functions of CD8+ TRM cells exhibit significant heterogeneity.MethodsThe roles and anti-tumor biological functions of different CD8+ TRM subsets in CRC were determined by clinical CRC samples, bioinformatics analysis, and in vitro experiments including co-culture experiments and transwell migration assays. The signaling pathways that synergistically regulate the differentiation of CD8+ TRM cells were identified by in vitro CD8+ T cell activation and inhibition assays, and the functioning transcription factors were predicted using the UCSC and JASPAR databases.ResultsWe found that different CD8+ TRM subsets existed in CRC tumor tissues, which were identified as CD69-CD103-CD8+ TRM, CD69+CD103-CD8+ TRM (SP CD8+ TRM), and CD69+CD103+CD8+ TRM (DP CD8+ TRM) subsets. Compared with SP CD8+ TRM cells, increased infiltration of DP CD8+ TRM cells predicted better prognosis and played a protective role mainly in tumor invasion and lymph node metastasis of CRC. DP CD8+ TRM cells expressed higher levels of effector molecules and exerted stronger anti-tumor effects in a FAS/FASL pathway-dependent manner. Additionally, DP CD8+ TRM cells secreted higher levels of CXCL13 and recruited B cells into tumor tissues through the CXCL13/CXCR5 signaling axis to form tertiary lymphoid structures, participating in anti-tumor immune responses. Notch and TGF-beta signaling pathways synergistically regulate the differentiation of DP CD8+ TRM cells.ConclusionsWe clarified the roles and mechanisms of different CD8+ TRM subsets in CRC and identified that DP CD8+ TRM cells exert stronger anti-tumor effects and predict better prognosis, which provides ideas for developing new clinically available therapeutic targets.

引用

页数：17

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